Principal Investigator George H De Vries Title Promotion of Functional Recovery From Demyelinating Disease KeyWords Exp. Autoimmune Enceph. MS, Demyelinating Diseases, Inflammation. Purpose- Functional loss after demyelination is a one of the major problems of veterans seeking treatment at VA medical centers. It is estimated that currently there are 20,000 veterans who are actively receiving treatment for multiple sclerosis (MS) which is the major demyelinating disease affecting young adults. Often MS begins as a series of exacerbations and remissions which eventually over a period of years resolves into a progressive course with no remissions. Current FDA treatments are focused on decreasing the number and frequency of exacerbations. Our hypothesis is: Functional recovery from chronic demyelination can be achieved by recruiting intact neurons in the CNS to sprout and restore function to the lost pathways (neuroplasticity). In order to test this hypothesis we will develop a model of chronic focal demyelination (targeted EAE-tEAE) developed in our laboratory which results in the functional loss of a behavioral task in our case a skilled forelimb retrieval task. Plasticity will be evaluated by labeling the contralateral intact pathway and determining the degree to which the labeled fibers attempt to sprout and take over lost function by crossing the midline. This measure of plasticity has been successfully used in the stroke model by our collaborator Dr. G. Kartje. Functional recovery will be evaluated as a measure of neuroplasticity. There are three two objectives for the proposed research: 1. To develop and characterize a t-EAE model in which there is a persistent immune-mediated lesion. 2.To evaluate the ability of the rat rehabilitation plus enriched enviorment to promote recovery after t-EAE It is anticipated that the results of this study will form the basis for the use and evaluation of the other strategies to enhance neuroplasticity which combined with rehabilitation will quickly and effectively promote functional recovery.